Metabolomics is the study of the chemical fingerprints or metabolites associated with various chemical processes occurring within tissues and fluids of various biological organisms. These chemical fingerprints are a result of specific cellular processes that leave behind specific metabolic, or small-molecule metabolite, profiles. The metabolome is the collection of all metabolites in a biological cell, tissue, organ, or organism. These metabolites are the end products of these various cellular processes.
Nuclear Magnetic Resonance (NMR) spectroscopy is a quantitative, non-destructive method that requires no, or minimal, sample preparation and is one of the leading analytical tools for metabonomics (metabolomics) research. 1H NMR is especially attractive because protons are present in virtually all metabolites and their NMR sensitivity is high, enabling simultaneous identification and monitoring of a wide range of low molecular weight metabolites and provide a biochemical fingerprint of an organism. However, the resolution of the 1H NMR spectra from tissues is often poor due to magnetic susceptibility variations, as well as other residual proton dipolar coupling and residual chemical shift anisotropy interactions. Further, MAS typically requires tissue samples of between 10 mg and 40 mg, or volumes of a few μL, or more, for standard metabolic profiling, which limits possible applications. Often small animals need to be sacrificed to obtain adequate amounts of tissues or blood for analysis. This makes it difficult or impossible to carry out continuous studies on single animals over a long period of time. And, changes to metabolite biomarkers due to normal biological variations often requires a large number of animals in order to provide sufficient biostatistical data, making metabolomics investigations expensive. The unique ability of MAS to analyze intact tissue samples eliminates the extraction process, which is a major breakthrough in metabolomics, not only because the extraction takes time, but also because metabolites can be lost during the extraction process. The MAS technique generates a high resolution 1H NMR metabolite spectrum of tissue samples with spectral resolution approaching that obtained from standard liquid-state NMR on cell and tissue extracts. And, various line broadening mechanisms can be eliminated at a sample spinning rate of several kHz or more. Recently, several new miniaturization approaches have been introduced in the art that report to decrease sample sizes for the MAS technique. However, various weaknesses have been identified in these approaches including, e.g., coil designs that induce line broadening and seriously reduce sensitivity at low spinning rates of current interest, suitability for solid-state analyses only, and other demonstrated weaknesses.
Accordingly, new devices and methods are needed that address various problems known in the art, and can perform metabolic profiling on small intact biological samples so that non-invasive and/or minimally invasive detection and analyses are possible. The present invention addresses these needs. Additional advantages and novel features of the present invention will be set forth as follows and will be readily apparent from the descriptions and demonstrations set forth herein. Accordingly, the following descriptions of the present invention should be seen as illustrative of the invention and not as limiting in any way.